This is a Phase I study of the farnesyltransferase inhibitor, L-778,123 with radiotherapy in patients with lung cancer, head and neck cancer, and pancreatic cancer. Hypothesis is the administration of L-778, 123 for two two week periods in combination with standard radiotherapy at a dose that achieves steady state plasma concentrations of at least 2.0 uM will be generally safe and well tolerated in patients with locally advanced malignancies. The objectives of the study are: Primary: (1) Evaluate the safety and tolerability of L-778,123 including determination of the maximally tolerated dose (MTD), when administered for weeks 1, 2, 4, and 5 of radiotherapy for pancreatic cancer. (2) Define the Recommended Phase II Dose (RPTD) when L-778,123 is administered for Weeks 1 to 5 of radiotherapy for pancreatic cancer. Secondary: (1) Evaluate the safety and tolerability of L-778,123 including determination of the maximally tolerated dose (MTD), when administered for weeks 1, 2, 4, and 5 of radiotherapy for head and neck or non-small cell lung cancer. (2) Define the Recommended Phase II Dose (RPTD) when L-778,123 is administered for Weeks 1 to 5 of radiotherapy for head and neck or non-small lung cancer. (3) Evaluate radiologic or tumor marker responses to treatment with L-778,123. (4) Evaluate the relationship between ras mutations and response to treatment with L-778,123. (5) Evaluate the relationship between plasma drug levels and farnesylation assay results.